Transcription
You probably noticed that the title of this lecture section is not atherosclerosis but arterioclerosis, and that is not a mistake because we will be talking more generally about arterioclerosis and its different types. This means that atherosclerosis is just one type of arterioclerosis, although it is the most common one. Arterioclerosis itself is a general term describing the thickening of arterial walls and loss of elasticity.
Of course, in this part of the lecture, we will mostly focus on atherosclerosis, which is a specific type of arterioclerosis caused by the accumulation of cholesterol and fat deposits on the vessel wall. Well, this also means that you need to be a bit careful when using these terms, as we will introduce a few more and it is easy to mix them up. Atherosclerosis itself is a chronic inflammatory disease and it mainly affects large and medium-sized arteries.
The most common locations where atherosclerosis occurs are listed here, but be careful in a descending order. So, the most frequent site is the carotid artery, and in this list, the least common location is the abdominal aorta. So, carotid artery comes first, and now we will move on to the pathology of atherosclerosis.
First, let's look at the risk factors. We can divide risk factors into two main groups: those that we can influence and change, and those that we cannot influence. Among the modifiable risk factors, we include hypertension or elevated blood pressure, diabetes mellitus (both types actually, although only the second one is probably modifiable), smoking, and dyslipidemia. Dyslipidemia refers to a disorder of lipid metabolism in the blood, most commonly involving cholesterol and triglycerides. It is usually characterized by an increase in low-density lipoproteins and a decrease in high-density lipoproteins. In simple terms, LDL is called the "bad cholesterol" and HDL the "good cholesterol."
On the other hand, the non-modifiable risk factors, which we cannot change, include age (with higher risk typically above 45 years in men and 55 years in women), genetic predisposition, and ethnic background (for example, African American origin).
Now, moving on to the pathogenesis itself. Atherosclerosis can essentially be described as an inflammatory response to damaged endothelium. The endothelium becomes damaged because of arterioclerosis in general, since the vessel wall becomes stiffer, and due to this damaged endothelium, low-density lipoprotein particles are able to enter the vessel in the site of injury, and this is where inflammation begins. Accordingly, macrophages begin to act. They don't just attempt to, but they actually phagocytose these low-density lipoprotein particles. And after this phagocytosis has taken place, the macrophages become filled with lipid particles. These lipid-filled macrophages are then called foam cells, and they accumulate at the site of damage. So, here we will have many, many macrophages. The accumulation of these foam cells leads to the formation of fatty streaks in the vessel wall. These fatty streaks are precursors of atherosclerotic plaques. In fact, this is the earliest sign of atherosclerosis, although at this stage, there are still no clinical symptoms. So, we have these fatty streaks, and they still do not cause symptoms. For example, they do not yet cause angina.
However, these fatty streaks unfortunately attract platelets. The platelets then respond by releasing various substances, which you don't need to memorize in detail, but all of them are generally classified as growth factors, and as the name suggests, growth factors stimulate growth. So, what happens next? What actually starts to grow is the smooth muscle. Growth factors stimulate the proliferation and migration of smooth muscle cells. Once these smooth muscle cells have spread, they begin to change because they are now in an atypical location. So, they transform into fibroblast-like cells. Well, not exactly fibroblasts, but very similar, and they acquire many of their functions. Let me remind you that fibroblasts were the main cells of connective tissue. So, but these cells, these fibroblast-like cells, begin to produce large amounts of extracellular matrix, similar to fibroblasts. So, including collagen, elastic fibers, and glycosaminoglycans. These are all components, as you know, of connective tissue. In other words, the smooth muscle cell starts producing connective tissue. Inside this extracellular matrix, in the central core, there are lipids forming a lipid core. At this stage, we already call this structure an atherosclerotic plaque, although it hasn't penetrated the blood vessel lumen yet. The lipid core is made up of cholesterol crystals, and initially, it is separated from the vessel lumen by connective tissue. Such a plaque can actually remain in the vessel wall for many years without causing any symptoms.
However, over time, the foam cells, which are within the plaque here (because we still have these foam cells, which were macrophages previously, within the plaque), and over time, they undergo necrosis. Now, so when this necrosis occurs, more and more lipids are released into the vessel lumen, because you have to take into account that these foam cells, now dead foam cells, were previously macrophages. So, originally, they were phagocytic cells. So, they contain a large number of enzymes within them, and over time, enzymes from the dead foam cells, which are also released when the cells die, begin to break down the connective tissue that separated the plaque from the vessel lumen. So, the enzymes within the macrophages are exactly what now damages and weakens this connective tissue layer. As a result, the lipid mass becomes exposed and enters the vessel lumen. The platelets then react to this because it is recognized as a foreign surface. And this, you probably already know, when platelets encounter such a surface, they initiate the hemostasis process, which we already know then. And here, of course, a thrombus forms, which can partially block the blood vessel. From this thrombus, emboli, or from emboli, can also develop.
But this is not the only consequence and not the only reason why atherosclerosis is dangerous. Among the complications, we also include ischemia, but for ischemia to occur, typically at least 70% of the artery must be blocked. Additionally, if all of this happens in the coronary arteries, so if the coronary arteries are involved, one of the complications is angina pectoris. Just to remind you, angina is a pain or discomfort in the chest that occurs when the heart muscle does not receive enough oxygen-rich blood. Another interesting manifestation is claudication. This occurs when arteries, such as the popliteal artery, are narrowed or blocked. As a result, during physical activity, such as walking, the muscles do not receive enough oxygen, and this leads to pain and limping. But the symptoms usually disappear with rest. Of course, another complication is infarction, which we already discussed earlier. Although infarction can occur in any organ, the most common is myocardial infarction. Another complication is the formation of an aneurysm, most commonly in the abdominal aorta. An aneurysm is essentially a localized dilation of the vessel wall. It is more likely to occur where the arterial wall is weaker and thinner, and this is the case in the lower part of the body. In this case, the vessel wall becomes weaker, and in the worst-case scenario, it may even rupture. And finally, as I mentioned earlier, embolism can occur, but also fat embolism. This means that fragments of the cholesterol and lipid core can break off and travel through the bloodstream. These fragments often block vessels in the kidneys, and due to gravity, they can also end up in the smaller vessels of the lower extremities, where they may lead to gangrene. An interesting point is that fat embolism can be associated with eosinophilia, meaning an increased number of eosinophils in the blood, and also eosinophiluria, meaning eosinophils appearing in the urine. These can serve then as indicators that this process has occurred.
So, this is classical atherosclerosis. And now I will take a look at some other types of arteriosclerosis besides atherosclerosis. Now, this one will be quite fun to say: arteriosclerosis. So, the sclerosis of arteries. Be aware, we have an extra "l" here. So, be careful when reading or writing that word. So, this is also a type of arterioclerosis, but it affects smaller blood vessels. So, specifically the arterioles. There are two main types: hyaline and hyperplastic.
First, the hyaline type. What happens here? Lipids, this time, are not involved. Instead, proteins are deposited in the vessel wall. And there are usually two main risk factors: chronic hypertension and diabetes. In hypertension, what happens is that there is increased blood flow and increased pressure on the vessel walls, which leads to strong stretching of the blood vessel wall. This can be due either to this elevated flow or because the vessel itself is narrowed. So, vasoconstriction, or both, of course. In any case, this strong mechanical stress effectively pushes plasma proteins into the vessel wall. The result is that the arterial wall becomes thickened with these proteins. In diabetes, on the other hand, the excess glucose in the blood binds to plasma proteins. These altered proteins then also deposit in the vessel wall, leading to a similar result. In both cases, the outcome can be ischemia in small vessels and even infarction in the affected tissues. Unfortunately, one of the most common arteries affected by this are brain arteries.
Now, the second type of arteriosclerosis is the hyperplastic type. It is caused by very high acute elevations in the blood pressure. Now, in other words, this is not about chronic, constantly elevated blood pressure, but rather about frequent spikes of very high blood pressure without it being constant. And due to these fluctuations in blood pressure, the basement membrane gradually thickens. This, in turn, leads to proliferation of smooth muscle cells, which begin to grow toward the lumen of the vessel and eventually can narrow it and even block it, as you see in the picture. This can be very clearly seen in histological samples. In pathology, this appearance is often compared to an onion skin pattern of the vessel wall. The arteries most commonly affected are those in the kidneys, retina, and intestines.
And finally, the last type of arteriosclerosis is one that actually is not pathological, but rather benign, but it is still worth mentioning it if we are talking about arterioclerosis in general. This one is called Mönckeberg sclerosis or medial calcific sclerosis. Well, you won't find very much information about this in pathology books, partly because, as I mentioned, it is not really considered a pathological condition. It is also relatively rare and rarely clinically significant, and it is most often described as a radiological finding. What happens here is that calcium salts are deposited in the middle layer of the artery. That's why medial calcific sclerosis. And this is the layer where the smooth muscle and connective tissue are located. This layer becomes calcified, and as a result, the vessel loses its elasticity. However, a very important point is that the lumen of the vessel is not obstructed. So, although the vessel becomes less elastic, blood flow itself is not impaired. On imaging, especially X-ray, this can be clearly seen because calcium salts are highly visible. The arteries can take on a characteristic pipe-like appearance because the calcified walls become easily recognizable on radiological images.
So, to summarize, atherosclerosis is essentially the foundation of systemic circulatory pathology. In pathophysiology, we must not think of atherosclerosis only as plaques in the arteries. Of all types of arterioclerosis, this is, of course, the most common one encountered in clinical practice. And it is important to remember that it is a chronic, progressive, systemic disease with endothelial damage as its central mechanism. That means even if at rest the circulation seems normal and sufficient, in stress conditions such as surgery, hypothermia, or cardiopulmonary bypass, these vessels no longer have the ability to adapt properly. So, it is not so much that the blood flow is slower, but rather that the vessels have become rigid and non-elastic. As a result, the circulation itself also becomes less adaptable and cannot adjust effectively to changing conditions. So, that's about the blood vessels, and now it's probably time to move on to the heart.